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PhD ceremony Mr. S. Paul: PET-Imaging to measure therapy-related occupancy and disease-induced changes of expression of adenosine A1-receptors in the brain

When:Mo 24-03-2014 at 14:30
Where:Academiegebouw, Broerstraat 5, Groningen

PhD ceremony: Mr. S. Paul

Dissertation: PET-Imaging to measure therapy-related occupancy and disease-induced changes of expression of adenosine A1-receptors in the brain

Promotor(s): prof. R.A.J.O. Dierckx, prof. P.H. Elsinga

Faculty: Medical Sciences

The adenosine A1 receptor (A1R) is a protein with a widespread distribution in the human body. Stimulation of this protein may result in neuroprotection and suppression of neuroinflammation. Positron Emission Tomography (PET) is a powerful imaging tool which can be applied to investigate the (patho)physiologic roles of A1R in the brain of living rodents and human beings.

The thesis provides an introduction on adenosine A1R imaging and discusses roles of A1R in health and disease. We applied radiolabelled [11C]-MPDX for visualization of A1R in rat brain. A high uptake of radioactivity was noted in hippocampus, striatum, and cerebellum. We examined whether A1R binding by therapeutic drugs can be assessed with [11C]-MPDX and PET. For this purpose we used N6-cyclopentyladenosine (CPA) and caffeine. The antagonist caffeine showed a clear competition, but no measurable competition occurred after administration of the agonist CPA. Furthermore, we assessed changes of A1R expression in a rat model of encephalitis. PET data indicated significantly increased [11C]-MPDX binding in hippocampus, cerebellum and medulla which indicates increased expression of the A1R protein A1R appear to play an important role in the protection of neurons during the early phase of rodent encephalitis.

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